Burgess, H. | bioRxiv Science

bioRxiv2026

Corpus Callosum Dysgenesis impairs metacognition: evidence from multi-modality and multi-cohort replications

The corpus callosum is the largest commissure in the mammalian brain and plays a major role in supporting cognitive processes required for adapting to complex environments. Individuals born with Corpus Callosum Dysgenesis (CCD), characterized by malformations of the corpus callosum, commonly exhibit deficits in social navigation, abstract problem-solving, decision-making, and self-awareness. Metacognition is a key cognitive process that supports these functions; however, it has yet to be tested comprehensively in individuals with CCD. Over three experiments, and three CCD cohorts, we tested the impact of this neurodevelopmental disorder on perceptual accuracy, confidence judgements, and metacognitive efficiency using two variants of a Random Dot Kinematogram task within lab, online, and VR conditions. We found that individuals with CCD typically displayed normal perceptual accuracy but failed to adjust their confidence judgements in line with task difficulty. Computational modelling revealed that this difference was explained by lower metacognitive efficiency driven by consistently lower metacognitive sensitivity. Together, these results provide evidence that the corpus callosum plays a crucial role in supporting metacognition.

neuroscience↗

bioRxiv2019

A model to study NMDA receptors in early nervous system development

NMDA receptors (NMDARs) are glutamate-gated ion channels that play critical roles in neuronal development and nervous system function. Pharmacological antagonism is an invaluable tool to study NMDARs, but is experimentally limited. Here, we developed a model to study NMDARs in early development in zebrafish, by generating CRISPR-mediated lesions in the NMDAR genes, grin1a and grin1b, which encode the obligatory GluN1 subunits. While receptors containing grin1a or grin1b show high Ca2+ permeability, like their mammalian counterpart, grin1a is expressed earlier and more broadly in development than grin1b. Both grin1a-/- and grin1b-/- zebrafish are viable as adults. Unlike in rodents, where the grin1 knockout is embryonic lethal, grin1 double mutant fish (grin1a-/-; grin1b-/-), which lack all NMDAR-mediated synaptic transmission, survive until about 10 days post fertilization, providing a unique opportunity to explore NMDAR function during development and in generating behaviors. Many behavioral defects in the grin1 double mutant larvae, including abnormal evoked responses to light and acoustic stimuli, prey capture deficits and a failure to habituate to acoustic stimuli, are replicated by short-term treatment with the NMDAR antagonist MK-801, suggesting they arise from acute effects of compromised NMDAR-mediated transmission. Other defects, however, such as periods of hyperactivity and alterations in place preference, are not phenocopied by MK-801, suggesting a developmental origin. Taken together, we have developed a unique model to study NMDARs in the developing vertebrate nervous system.

neuroscience↗